It is also noteworthy that although macrophages and VEGF play an important role in GPR65 KO–mediated primary resistance to CAR T therapy, the distinct in vivo kinetics of GPR65-high m.CR and GPR65-low m.PR tumor cells studied here and the ultimate CD19− relapse observed in CAR T–treated m.PR tumor–engrafted mice illustrate the complexity of individual tumors and the TME and their mechanisms of resistance. This evidence concerns the gene GPR65 and neoplasm.